The invention relates to a new method for the preparation of N-protected 4-ketoproline derivatives.
N-protected 4-ketoproline derivatives of the general formula I are inter alia important starting compounds for the preparation of the ACE angiotensin-converting enzyme, inhibitor Spirapril [7-(N-(1-(S)-carbethoxy-3-phenylpropyl)-(S)-alanyl-1,4-dithia-7-azaspiro(4 ,4)nonan-8-(S)-carboxylic acid] of formula II, which is used for the treatment of high blood pressure and of cardiovascular disorders (U.S. Pat. No. 4,470,972). ##STR3##
Methods for the synthesis of 4-ketoproline derivatives of the general formula I are usually based on oxidizing agents containing heavy metals such as, for example, various chromium-containing oxidising systems (see U.S. Pat. No. 4,296,113) or RuO.sub.2 /NaOCl (see DD-A5 283 626). These methods have the disadvantage that they require additional safety measures during the carrying out of the reaction, as well as an elaborate and expensive removal of the heavy metals on completion of the reaction.
DD-A5 283 626 describes a method for the preparation of (2S)-N-benzyloxycarbony-4-ketoproline, which method does not involve heavy metals and uses as an oxidizing agent a sulphur trioxide-pyridine complex. This method has the disadvantage that, in using pyridine, one is likewise employing a substance which is very damaging to the environment and highly toxic for humans.